Sickle Cell Disease Research

Current research on sickle cell disease treatment

Many NHLBI-supported studies are looking at gene therapies and blood and marrow transplants (BMT) as transformative therapies for people with sickle cell disease.

NHLBI News

In December 2023, the FDA approved two gene therapies for some people with sickle cell disease. Everyone’s experience is different, but people treated with gene therapy tend to have less anemia, fewer health problems related to sickle cell, and better health-related quality of life. This important advance was built upon years of NHLBI-funded discoveries about the genes that cause sickle cell disease and affect disease severity and how best to perform gene therapy. 

Learn more about these life-changing therapies in a Q&A with two NHLBI leaders.

• Speeding progress on cures: The Cure Sickle Cell Initiative (CureSCi) is an NHLBI-led collaborative research effort to speed the development of gene therapies to treat sickle cell disease. CureSCi clinical trials focus on altering genes in patients’ own hematopoietic (blood-forming) stem cells so that the red blood cells do not sickle. Results from the first 10 participants in a phase 1 CureSCi clinical trial showed that a type of gene therapy was safe and effective for reducing pain crises. Based on that early success, a phase 2 trial of the same therapy began in 2024. 
• Developing medicines to help the blood work better: The NHLBI’s Sickle Cell Branch scientists conducted an early-stage study of a medicine called mitapivat in people with sickle cell disease. The study showed that mitapivat decreased red blood cell sickling and breakdown and could be safely used to improve hemoglobin levels. Based on the promising results, other research groups carried out longer studies with more participants. Those studies showed that participants who took mitapivat for a year had fewer pain crises, in addition to improved hemoglobin levels and less sickling of red blood cells.
• Making blood transfusions safer: Many patients with sickle cell disease often receive blood transfusions to treat and prevent certain complications. NHLBI-funded researchers are exploring how to optimize safety and benefits of blood transfusions for people living with the disease. 
• Evaluating monthly exchange red blood cell transfusions: As people with sickle cell disease become adults, they may develop heart and lung diseases that can cause early death. Blood and heart ultrasound tests can identify patients at risk for these complications. The Sickle Cell Disease and Cardiovascular Risk — Red Cell Exchange (SCD–CARRE) trial is testing monthly automated exchange transfusions as a strategy to reduce serious complications of sickle cell disease, improve symptoms, and prevent hospitalization and death. Exchange transfusions remove a person’s blood and replace it with red blood cells from a donor.
• Improving access to BMTs: The NHLBI collaborates with the National Cancer Institute in funding efforts to improve access to BMT through the BMT Clinical Trials Network. Several studies are exploring options for people with sickle cell disease who don’t have a well-matched donor who is a family member. For example, one study is comparing treatment of severe sickle cell disease with BMTs using cells from either an unrelated immune-matched donor or from a mismatched donor.

Find more NHLBI-funded studies on sickle cell disease treatment at NIH RePORTER. Information on NHLBI-supported sickle cell disease treatment clinical trials is also available.

Current research on managing sickle cell pain

• Exploring new ways to reduce the pain crises: Pain crises — also called sickle cell crises or vaso-occlusive crises — affect nearly all people with sickle cell disease. These crises are the leading cause of emergency department visits and hospitalizations for people with the disease. An NHLBI-funded study found that treating children with arginine could lower inflammation linked with sickle cell pain crises and lower the amount of opioid medicine needed to manage pain. 
• Promoting guideline-based care for sickle cell pain: Too often, healthcare providers in emergency departments do not follow guidelines for treating pain. This leads to delays in treatment, more pain, and more hospitalizations. In addition, racism may be a barrier to care. An NHLBI-supported study is testing a care pathway to promote guideline-based care for children being treated in emergency departments for pain crises. 
• Innovating approaches to reduce sickling: Through its Small Business Innovation Research program, the NHLBI is supporting the development of a nanoparticle-based therapy for sickle cell disease. Heparin is a medicine that shows some potential benefits for sickle cell disease, but it can raise the chance of bleeding. This project is testing a nanoparticle version of heparin in animal models and lab tests to learn whether the compound can lower sickling of red blood cells without unwanted side effects. If the project succeeds, the nanoparticle version of heparin will be readied for first-in-human studies. 
• Studying the role of gut bacteria in pain of sickle cell disease: NHLBI-funded scientists are studying the gut microbiome — microbes living in the intestines — of people with sickle cell disease. This is the first study of the role the microbiome may play in causing sickle cell pain crises and long-term pain. Other studies have shown that an out-of-balance microbiome can worsen the pain of some inflammatory diseases such as rheumatoid arthritis. 

Find more NHLBI-funded studies on pain management in sickle cell disease at NIH RePORTER.  Information on NHLBI-supported sickle cell disease pain related clinical trials is also available.

Current research into sickle cell trait

People with sickle cell disease have two genes for hemoglobin S. In contrast, people with sickle cell trait have one gene for hemoglobin S and another gene for normal hemoglobin A. Though most people who have sickle cell trait don’t have any symptoms, some may experience symptoms in rare situations. The NHLBI is supporting research to better understand health concerns that people who have sickle cell trait might face. 

• Studying health risks linked with sickle cell trait: Two NHLBI scientists reviewed evidence of links between sickle cell trait and various health problems. People with sickle cell trait live as long as people who don’t have the trait. The review included findings of a study of nearly 48,000 Black soldiers that showed that soldiers with sickle cell trait did not have higher rates of sudden death compared to soldiers without the trait. Sickle cell trait slightly raised the chance of rhabdomyolysis (muscle damage) with extreme exertion. Studies also suggest that sickle cell trait raises the chance of kidney disease and venous thromboembolism.
• Detecting early signs of dangerous blood clots: An NHLBI clinical trial is studying blood clotting and markers of inflammation in people with sickle cell trait or sickle cell disease to identify risk factors for venous thromboembolism. The researchers are comparing data from people who have had venous thromboembolism and people who do not have the condition to find possible links with sickle cell disease or trait. 

Current research to improve access to care for sickle cell disease 

Despite their extensive healthcare needs, many people living with sickle cell disease have difficulty getting appropriate care. People often report feeling stigmatized and having their symptoms dismissed when they do seek care. The NHLBI is committed to research that will help lower the barriers patients face when seeking sickle cell disease treatment and trying to stick with their treatment plan. 

• Understanding transitions in care for sickle cell disease: NHLBI-funded researchers looked at health records of 472 young people between 18 and 24 years old who received care for sickle cell disease at an Alabama clinic. The scientists checked to see how many engaged with adult care for sickle cell disease after receiving care in a pediatric clinic. The scientists found that less than half of the participants successfully transferred to adult care. Factors that led to successful transfers included engaging with pediatric and adult care at the same hospital, and being treated with hydroxyurea or blood transfusions. Many of those who did not transfer to adult clinics had dropped out of care by 15 years old. Read more about the study.
• Finding ways to help children continue hydroxyurea treatment: In 2014, the NHLBI published treatment guidelines that recommended offering hydroxyurea to all children and youth over 9 months old who have sickle cell disease. However, a study in New York State and Michigan found that only 1 in 3 children were taking this important medicine as prescribed. The scientists suggested that education programs for healthcare providers and families might help more children stick with this lifesaving treatment.
• Overcoming barriers to lowering stroke risk in children with sickle cell disease: Sickle cell disease greatly increases the risk of stroke in children, but regular screenings and treatments can reduce stroke risk by more than 90%. The NHLBI-funded Dissemination and Implementation of Stroke Prevention Looking at the Care Environment (DISPLACE) study aimed to improve access to stroke screening for children with sickle cell disease. DISPLACE researchers identified factors that are barriers to effective stroke screening, such as challenges in scheduling ultrasound scans, a need for appointment reminders, and a lack of information and education about stroke screening. Only about half of children received recommended ultrasound scans. The scientists also noted the need to improve training of healthcare providers who perform and interpret the scans. The DISPLACE results are important for ensuring more consistent use of guideline-directed screening and treatment.
• Promoting education about genetic therapies for sickle cell disease: As part of the National Institutes of Health (NIH), the NHLBI supports efforts to help people understand the basics of hemoglobin disorders as well as transformative treatments. The NIH’s Sickle Cell Disease Gene Therapy Education Project provides educational materials to help people understand gene therapies so they can make informed decisions. The materials reflect the input of patients, parents of patients, healthcare providers, community-based organizations, advocacy groups, industry leaders, government representatives, and researchers. The website includes a set of FAQs that can help guide discussions between people with sickle cell disease and their providers.

Find NHLBI-funded studies on health disparities and sickle cell disease at NIH RePORTER. Explore health disparities sickle cell disease trials.

Researchers from the NHLBI Division of Intramural Research, which includes investigators in our Sickle Cell Branch, are focused on developing new treatments for sickle cell disease. The Sickle Cell Genetics and Pathophysiology Lab studies the genetic and biological factors underlying the variability of sickle cell disease symptoms and complications.

• NHLBI scientists are using the ReFRAME Drug Repurposing Library, which lists medicines that are approved by the FDA and have the potential to treat or prevent sickle cell pain crises at lower cost. By screening the medicines in the library, scientists discovered 106 compounds that stop sickling of hemoglobin. Further analysis showed that 21 compounds could be potential treatments to prevent pain crises. 
• The NHLBI set up the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) in 2008. BioLINCC has since expanded to include samples and data from more than 580,000 people participating in more than 180 studies. With the addition of the Cure Sickle Cell Hematopoietic Stem Cell Collection study in 2022, samples of stem cells and study data from people with sickle cell disease became available to support research. 

Read more about these projects and ongoing clinical trials.

The NHLBI leads and supports many programs and initiatives around the nation and the world as we work to improve the lives of people with sickle cell disease.

The NHLBI Hosted 2023 Conference on Sickle Cell Disease

The 16th annual 2023 Sickle Cell in Focus (SCiF) conference was held in October 2023 and co-hosted by the NHLBI and the University of West Indies. View video recordings of the 2023 conference: 

• Day 1, October 10: https://videocast.nih.gov/watch=52475 
• Day 2, October 11: https://videocast.nih.gov/watch=52477

Registration is open for the 17th conference to be held in September 2024.

• The  Recipient Epidemiology and Donor Evaluation Study Program tests transfusion therapies and improves their safety and success. The program also works to address potential emerging threats to the United States’ blood supply and serves as a resource for work in transfusion research.
• The NHLBI has taken a lead role in managing the Regenerative Medicine Innovation Project under the 21st Century Cures Act. Beginning in 2017, the Act authorized the investment of $30 million in clinical research with adult stem cells to treat diseases, including sickle cell disease.
• Most people who have sickle cell disease live in Africa. The NHLBI supports three major programs in sub-Saharan Africa across 9 countries and 11 cities. The Sickle Pan-African Research Consortium, the Sickle Cell Disease Genomics Network of Africa (SickleGenAfrica), and Realizing Effectiveness Across Continents with Hydroxyurea (REACH) are all working to build research capacity and enhance disease surveillance and delivery of care. Their efforts have led to successes: 
  • The Sickle Pan-African Research Consortium demonstrated that widespread newborn screening for sickle cell disease is possible is sub-Saharan Africa.
  • The SickleGenAfrica Network developed an ethics framework and presented findings from community engagement in Ghana, Nigeria, and Tanzania.
  • REACH researchers found that hydroxyurea treatment is linked with lower malaria incidence in children with sickle cell anemia in sub-Saharan Africa. 

NHLBI Annual Conference Highlights Recent Advances in Sickle Cell Disease Research and Care 

The yearly NHLBI Sickle Cell Disease Research Meeting is a forum for scientists and healthcare providers to learn about ongoing research in the scientific and clinical aspects of the disease. View recordings of the 3-day, 2024 meeting:

• Day 1, August 12: https://videocast.nih.gov/watch=54991 
• Day 2, August 13: https://videocast.nih.gov/watch=54992 
• Day 3, August 14: https://videocast.nih.gov/watch=54993